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- Title
Molecular mechanism for the enhancement of arbekacin resistance in a methicillin-resistant Staphylococcus aureus
- Authors
Matsuo, Hiroaki; Kobayashi, Miho; Kumagai, Takanori; Kuwabara, Masao; Sugiyama, Masanori
- Abstract
We have clinically isolated a methicillin-resistant Staphylococcus aureus (MRSA) K-1 which exhibits enhanced arbekacin (Abk) resistance. In this study, we investigated a molecular mechanism for the overproduction of a bifunctional enzyme catalyzing both 2″-O-phosphorylation and 6′-N-acetylation of aminoglycoside antibiotics that is encoded by aacA-aphD and designated [AAC(6′)/APH(2″)] and is expressed in MRSA K-1. The sequence analysis of the 5′-adjacent region of the aacA-aphD structural gene in MRSA K-1 showed that 12 bp are deleted from the aacA-aphD promoter region when compared with that in MRSA B-26, which exhibits lower resistance to Abk than K-1. By artificially deleting the 12 bp from the corresponding region in MRSA B-26, we confirmed that the strain increases Abk resistance to the same level as seen in MRSA K-1, which suggests that the 12 bp deletion from the 5′-adjacent region of the aacA-aphD structural gene created a strong promoter to overexpress the bifunctional enzyme.
- Subjects
STAPHYLOCOCCUS aureus; PHOSPHORYLATION
- Publication
FEBS Letters, 2003, Vol 546, Issue 2/3, p401
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/S0014-5793(03)00644-6